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1.  Markers of Oxidant Stress that are Clinically Relevant in Aging and Age-related Disease 
Despite the long held hypothesis that oxidant stress results in accumulated oxidative damage to cellular macromolecules and subsequently to aging and age-related chronic disease, it has been difficult to consistently define and specifically identify markers of oxidant stress that are consistently and directly linked to age and disease status. Inflammation because it is also linked to oxidant stress, aging, and chronic disease also plays an important role in understanding the clinical implications of oxidant stress and relevant markers. Much attention has focused on identifying specific markers of oxidative stress and inflammation that could be measured in easily accessible tissues and fluids (lymphocytes, plasma, serum). The purpose of this review is to discuss markers of oxidant stress used in the field as biomarkers of aging and age-related diseases, highlighting differences observed by race when data is available. We highlight DNA, RNA, protein, and lipid oxidation as measures of oxidative stress, as well as other well-characterized markers of oxidative damage and inflammation and discuss their strengths and limitations. We present the current state of the literature reporting use of these markers in studies of human cohorts in relation to age and age-related disease and also with a special emphasis on differences observed by race when relevant.
doi:10.1016/j.mad.2013.02.008
PMCID: PMC3664937  PMID: 23428415
DNA oxidation; RNA oxidation; Protein oxidation; Single Strand Breaks; CRP
2.  Genetic Variants in Platelet Factor 4 Modulate Inflammatory and Platelet Activation Biomarkers 
Circulation. Cardiovascular genetics  2012;5(4):10.1161/CIRCGENETICS.111.961813.
Background
African Americans suffer from higher prevalence and severity of atherosclerosis compared to Whites, highlighting racial and ethnic disparities in cardiovascular disease. Previous studies have pointed to the role of vascular inflammation and platelet activation in the formation of atherosclerotic lesions.
Methods and Results
We explored the role of genetic variation in four chemokine/chemokine receptor genes (CX3CR1, CX3CL1, CXCR3 and PF4) on systemic inflammation and platelet activation serum biomarkers (fractalkine, platelet P-selectin, PF4 and TNFα). In total, 110 SNPs were tested among 1,042 African Americans and 763 Whites. The strongest association with serum PF4 levels was observed for rs168449, which was significant in both racial groups (P-value: African Americans=0.0017, Whites=0.014, Combined=1.2×10−4), and remained significant after permutation-based multiple corrections (Pc-value: Combined=0.0013). After accounting for the effect of rs168449, we identified another significant SNP (rs1435520) suggesting a second independent signal regulating serum PF4 levels (conditional P-value: African Americans=0.02, Whites=0.02). Together these SNPs explained 0.98% and 1.23% of serum PF4 variance in African Americans and Whites, respectively. Additionally, in African Americans, we found an additional PF4 variant (rs8180167), uncorrelated with rs168449 and rs1435520, associated with serum TNFα levels (P-value=0.008, Pc-value=0.048).
Conclusions
Our study highlight the importance of PF4 variants in the regulation of platelet activation (PF4) and systemic inflammation (TNFα) serum biomarkers.
doi:10.1161/CIRCGENETICS.111.961813
PMCID: PMC3864008  PMID: 22763266
association study; atherosclerosis; inflammation; platelets; Chemokines; PF4; TNF-alpha
3.  Coordination of DNA repair by NEIL1 and PARP-1: a possible link to aging 
Aging (Albany NY)  2012;4(10):674-685.
Oxidative DNA damage accumulates with age and is repaired primarily via the base excision repair (BER) pathway. This process is initiated by DNA glycosylases, which remove damaged bases in a substrate-specific manner. The DNA glycosylases human 8-oxoguanine-DNA glycosylase (OGG1) and NEIL1, a mammalian homolog of Escherichia coli endonuclease VIII, have overlapping yet distinct substrate specificity. Recently, we reported that OGG1 binds to the Poly(ADP-ribose) polymerase 1 (PARP-1), a DNA damage sensor protein that poly(ADP-ribosyl)ates nuclear proteins in response to DNA damage and other cellular signals. Here, we show that NEIL1 and PARP-1 bind both in vitro and in vivo. PARP-1 binds to the C-terminal-100 amino acids of NEIL1 and NEIL1 binds to the BRCT domain of PARP-1. NEIL1 stimulates the poly(ADP-ribosyl)ation activity of PARP-1. Furthermore, NEIL-deficient fibroblasts have impaired poly(ADP-ribosyl)ation of cellular proteins after DNA damage, which can be rescued by NEIL1 expression. Additionally, PARP-1 inhibits NEIL1 incision activity in a concentration-dependent manner. Consistent with the idea of impaired DNA repair during aging, we observed differential binding of PARP-1 to recombinant NEIL1 in older mice compared to younger mice. These data further support the idea that dynamic interplay between different base excision repair proteins is important for efficient BER.
PMCID: PMC3517938  PMID: 23104860
PARP; base excision repair; DNA damage; oxidative stress; aging; glycosylase
4.  Age-related changes in microRNA levels in serum 
Aging (Albany NY)  2013;5(10):725-740.
microRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally regulate gene expression by targeting specific mRNAs. Altered expression of circulating miRNAs have been associated with age-related diseases including cancer and cardiovascular disease. Although we and others have found an age-dependent decrease in miRNA expression in peripheral blood mononuclear cells (PBMCs), little is known about the role of circulating miRNAs in human aging. Here, we examined miRNA expression in human serum from young (mean age 30 years) and old (mean age 64 years) individuals using next generation sequencing technology and real-time quantitative PCR. Of the miRNAs that we found to be present in serum, three were significantly decreased in 20 older individuals compared to 20 younger individuals: miR-151a-5p, miR-181a-5p and miR-1248. Consistent with our data in humans, these miRNAs are also present at lower levels in the serum of elderly rhesus monkeys. In humans, miR-1248 was found to regulate the expression of mRNAs involved in inflammatory pathways and miR-181a was found to correlate negatively with the pro-inflammatory cytokines IL-6 and TNFα and to correlate positively with the anti-inflammatory cytokines TGFβ and IL-10. These results suggest that circulating miRNAs may be a biological marker of aging and could also be important for regulating longevity. Identification of stable miRNA biomarkers in serum could have great potential as a noninvasive diagnostic tool as well as enhance our understanding of physiological changes that occur with age.
PMCID: PMC3838776  PMID: 24088671
circulating; miRNA; noncoding RNA; age; aging; biomarker; exRNA; extracellular RNA
5.  Sex Differences in Associations of Depressive Symptoms with Cardiovascular Risk Factors and Metabolic Syndrome among African Americans 
Young to middle-aged women usually have notably lower rates of cardiovascular disease (CVD) than their male counterparts, but African American women lack this advantage. Their elevated CVD may be influenced by sex differences in associations between depressed mood and CVD risk factors. This cross-sectional study examined whether relations between scores on the Center for Epidemiologic Studies-Depression (CES-D) scale and a spectrum of CVD risk factors varied by sex among African Americans (n = 1076; ages 30–64) from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. Sex-stratified multiple regressions and logistic regressions were conducted. Among women, CES-D scores correlated positively with systolic blood pressure and waist-to-hip ratio (P's < .05), but inversely with high-density lipoprotein cholesterol (HDL-C) (P < .01). Women had twice the odds for metabolic syndrome if CES-D scores ≥16 and had a ≥14% increase in odds of hypertension, abdominal obesity, and low HDL-C with each 5-unit increase in CES-D scores. Among men, CES-D scores correlated positively with high-sensitivity C-reactive protein (P < .05), and odds of hypertension increased by 21% with each 5-unit increase in CES-D scores. Depressive symptoms may promote premature CVD risk in African Americans, at least in part, via CVD risk factors and prevalent metabolic syndrome, particularly in African American women.
doi:10.1155/2013/979185
PMCID: PMC3787626  PMID: 24151548
6.  A novel R229Q OGG1 polymorphism results in a thermolabile enzyme that sensitizes KG-1 leukemia cells to DNA damaging agents 
Cancer detection and prevention  2007;31(3):237-243.
Background
Mutations and polymorphisms of OGG1, the major mammalian 8-oxoguanine repair activity, are associated with increased risk for several cancers. Decreased 8-oxoguanine repair capacity due to variant forms of the OGG1 gene is a common feature of numerous cancer cell lines. One such cell line, human KG-1 leukemia cells, has previously been demonstrated to be deficient in the excision of 8-oxoguanine from oxidatively damaged DNA. KG-1 cells have a homozygous R229Q amino acid substitution in OGG1 that has been presumed to alter the function of OGG1 and result in elevated levels of genomic 8-oxoG and hypersensitivity to 8-hydroxydeoxyguanosine nucleoside and ionizing radiation observed in KG-1 cells.
Methods
We characterized the enzymatic activity of R229Q OGG1 and the effect of the enzyme on cell survival following treatment with DNA damaging agents.
Results
R229Q OGG1 had activity similar to the wild-type enzyme, yet was easily heat inactivated at physiological temperature. R229Q OGG1 expressed in human cells had significantly lower activity than wild-type OGG1 and was also highly thermolabile. Expression of R229Q OGG1 sensitized KG-1 cells to killing by menadione and 8-hydroxydeoxyguanosine, but not ionizing radiation.
Conclusions
These results suggest that decreased 8-oxoguanine repair in KG-1 is due to thermolability of R229Q OGG1 and that the enzyme variant increases cellular susceptibility to killing resulting from oxidative DNA damage. The R229Q OGG1 variant is a validated polymorphism prevalent in world populations and not an isolated mutation in KG-1 cells, thus the R229Q OGG1 allele may be a novel marker for cancer susceptibility.
doi:10.1016/j.cdp.2007.05.001
PMCID: PMC2699023  PMID: 17651912
R229Q; OGG1; 8-oxoguanine; KG-1; leukemia; polymorphism
7.  OGG1 is degraded by calpain following oxidative stress and cisplatin exposure 
DNA repair  2008;7(4):648-654.
Deficient repair activity for 8-hydroxy-2′-deoxyguanine (8-oxoguanine), a premutagenic oxidative DNA damage, has been observed in affected tissues in neurodegenerative diseases of aging, such as Alzheimer’s disease, and in ischemia/reperfusion injury, type 2 diabetes mellitus, and cancer. These conditions have in common the accumulation of oxidative DNA damage, which is believed to play a role in disease progression, and loss of intracellular calcium regulation. These observations suggest that oxidative DNA damage repair capacity may be influenced by fluctuations in cellular calcium. We have identified human 8-oxoguanine-DNA glycosylase 1 (OGG1), the major 8-oxoguanine repair activity, as a specific target of the Ca2+-dependent protease Calpain I. Protein sequencing of a truncated partially calpain-digested OGG1 revealed that calpain recognizes OGG1 for degradation at a putative PEST (Proline, Glutamic acid, Serine, Threonine) sequence in the C-terminus of the enzyme. Co-immunoprecipitation experiments showed that OGG1 and Calpain I are associated in human cells. Exposure of HeLa cells to hydrogen peroxide or cisplatin resulted in the degradation of OGG1. Pretreatment of cells with the calpain inhibitor calpeptin resulted in inhibition of OGG1 proteolysis and suggests that OGG1 is a target for calpain-mediated degradation in vivo during oxidative stress- and cisplatin-induced apoptosis. Polymorphic OGG1 S326C was comparatively resistant to calpain digestion in vitro, yet was also degraded by a calpain-dependent pathway in vivo following DNA damaging agent exposure. The degradation of OGG1 by calpain may contribute to decreased 8-oxoguanine repair activity and elevated levels of 8-oxoguanine reported in tissues undergoing chronic oxidative stress, ischemia/reperfusion and other cellular stressors known to produce perturbations of intracellular calcium homeostasis which activate calpain.
doi:10.1016/j.dnarep.2008.01.003
PMCID: PMC2699025  PMID: 18294929
OGG1; calpain; 8-oxoguanine; calcium; PEST
8.  Cardiovascular Emotional Dampening: The Relationship between Blood Pressure and Recognition of Emotion 
Psychosomatic medicine  2011;73(9):743-750.
Objective
Persons with elevated blood pressure show dampened emotional responses to affect-laden stimuli. We sought to further examine cardiovascular emotional dampening by examination of the relationship between resting hemodynamic measures and recognition of emotion in an African-American community-based sample.
Methods
Participants were 106 African American men and women (55 female; mean age 52.8 years), mainly low in socioeconomic status and part of the Healthy Aging in Nationally Diverse Longitudinal Samples (HANDLS-Pilot) Pilot Study. Participants evaluated emotional expressions in faces and in sentences using the Perception of Affect Test (PAT). Resting blood pressure, total peripheral resistance (TPR), cardiac output and heart rate were obtained continuously using a Portapres blood pressure monitor.
Results
Total PAT scores were inversely related to systolic (r = −.30) and diastolic (r = −.24) blood pressure, TPR (r = −.36) and age (r = − .31; p values < .01), and positively related to cardiac output (r = .27) and education (r = .38; p values <.01), and with mental state (r = .25) and body mass index (r = −.20; p values < .05). Accuracy of emotion recognition on the PAT tasks remained inversely related to TPR and blood pressure after adjustment for demographic variables, medication, mental state and body mass index.
Conclusions
Elevated blood pressure and TPR were associated with reduced perception of affect. TPR was the most consistent independent hemodynamic correlate of emotional dampening for the PAT scores. These results suggest potentially important links among CNS regulation of emotions, hemodynamic processes and hypertension development.
doi:10.1097/PSY.0b013e318235ed55
PMCID: PMC3210914  PMID: 22042880
Emotion regulation; blood pressure; hemodynamics; hypertension development; central nervous system; stress
9.  Serum ferritin levels associated with increased risk for developing CHD in a low-income urban population 
Public health nutrition  2012;15(7):1291-1298.
Objective
The present study examined the association of serum ferritin with CHD risk using the Framingham Heart Study's 10-year risk algorithm.
Design
Ordinal logistic regression modelling was used to interpret risk. Proportional odds modelling assessed four divisions of ranked CHD risk (4, high; 3, increased; 2, slight; 1, minimal), separately by sex.
Setting
Baltimore, MD, USA.
Subjects
African-American and white participants (n 1823) from baseline of the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study, aged 30–64 years.
Results
For men, there was a 0.5% increase in risk for every 10-unit rise in serum ferritin (pmol/l). Other significant predictors included increased BMI, white race, unemployment and C-reactive protein ≥9.5 mg/l. For women, there was a 5.1% increase in risk per 10-unit rise in serum ferritin (pmol/l). Other significant predictors included increased BMI, lower education, unemployment and C-reactive protein ≥9.5 mg/l.
Conclusions
Serum ferritin is a significant predictor of 10-year hard CHD risk for HANDLS study participants, a low-income, urban population. Serum ferritin, independent of elevated C-reactive protein, was associated with increased 10-year CHD risk for HANDLS participants. To our knowledge, these data provide the first evidence of the role of serum ferritin as a risk factor for hard CHD in African-American and white postmenopausal women in the USA. Future research on cardiovascular events from this prospective study may confirm the association.
doi:10.1017/S1368980011003284
PMCID: PMC3445714  PMID: 22230289
CVD; Cohort study; Serum ferritin; CHD; Iron
10.  Symptoms of Posttraumatic Stress Disorder Among Urban Residents 
Previous studies indicate a high risk of Posttraumatic Stress Disorder (PTSD) among women and low-income, urban-residing African Americans. This study examined PTSD symptoms among urban-residing, socioeconomically diverse, working age, African Americans and whites. Participants completed the PTSD Checklist-Civilian Version. Of the 2,104 participants, 268 (12.7%) screened positive for PTSD symptoms. Women (13.8%) were more likely than men (11.3%), white participants (13.8%) were more likely than African Americans (11.9%), and younger participants (16.1%) were more likely than older (10.2%) to screen positive for PTSD symptoms. A significant interaction (p = .05) revealed that white women living below the 125% poverty level were most likely to report PTSD symptoms. These findings highlight the importance of PTSD screening in low-income, urban neighborhoods.
doi:10.1097/NMD.0b013e3182214154
PMCID: PMC3138132  PMID: 21716054
Symptoms of Posstraumatic Stress Disorder; civilians; urban residents
11.  A Meta-Analysis and Genome-Wide Association Study of Platelet Count and Mean Platelet Volume in African Americans 
PLoS Genetics  2012;8(3):e1002491.
Several genetic variants associated with platelet count and mean platelet volume (MPV) were recently reported in people of European ancestry. In this meta-analysis of 7 genome-wide association studies (GWAS) enrolling African Americans, our aim was to identify novel genetic variants associated with platelet count and MPV. For all cohorts, GWAS analysis was performed using additive models after adjusting for age, sex, and population stratification. For both platelet phenotypes, meta-analyses were conducted using inverse-variance weighted fixed-effect models. Platelet aggregation assays in whole blood were performed in the participants of the GeneSTAR cohort. Genetic variants in ten independent regions were associated with platelet count (N = 16,388) with p<5×10−8 of which 5 have not been associated with platelet count in previous GWAS. The novel genetic variants associated with platelet count were in the following regions (the most significant SNP, closest gene, and p-value): 6p22 (rs12526480, LRRC16A, p = 9.1×10−9), 7q11 (rs13236689, CD36, p = 2.8×10−9), 10q21 (rs7896518, JMJD1C, p = 2.3×10−12), 11q13 (rs477895, BAD, p = 4.9×10−8), and 20q13 (rs151361, SLMO2, p = 9.4×10−9). Three of these loci (10q21, 11q13, and 20q13) were replicated in European Americans (N = 14,909) and one (11q13) in Hispanic Americans (N = 3,462). For MPV (N = 4,531), genetic variants in 3 regions were significant at p<5×10−8, two of which were also associated with platelet count. Previously reported regions that were also significant in this study were 6p21, 6q23, 7q22, 12q24, and 19p13 for platelet count and 7q22, 17q11, and 19p13 for MPV. The most significant SNP in 1 region was also associated with ADP-induced maximal platelet aggregation in whole blood (12q24). Thus through a meta-analysis of GWAS enrolling African Americans, we have identified 5 novel regions associated with platelet count of which 3 were replicated in other ethnic groups. In addition, we also found one region associated with platelet aggregation that may play a potential role in atherothrombosis.
Author Summary
The majority of the variation in platelet count and mean platelet volume between individuals is heritable. We performed genome-wide association studies in more than 16,000 African American participants from seven population-based cohorts to identify genetic variants that correlate with variation in platelet count and mean platelet volume. We observed statistically significant evidence (p-value<5×10−8) that 10 genomic regions were associated with platelet count and 3 were associated with mean platelet volume. Of the regions that were significantly associated, we found 5 novel regions that were not reported previously in other populations. Three of these 5 regions were also associated with platelet count in European Americans and Hispanic Americans. All these regions contain genes that are either known to have or potentially may have a role in determining platelet count and/or mean platelet volume. We further found that one of these regions was also associated with agonist-induced platelet aggregation. Further studies will determine the exact role played by these genomic regions in platelet biology. The knowledge generated by this and other studies will not only help us better understand platelet biology but can also lead us to the discovery of new anti-platelet drugs.
doi:10.1371/journal.pgen.1002491
PMCID: PMC3299192  PMID: 22423221
12.  Receiver-operating characteristic of adiposity for metabolic syndrome: HANDLS study 
Public health nutrition  2010;14(1):77-92.
Objective
To assess the predictive values of various adiposity indices for the metabolic syndrome (MetS) among adults using baseline data from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) cohort.
Design
In a cross-sectional study, body mass index (BMI), waist circumference (WC), body composition by dual-energy x-ray absorptiometry (DXA) and metabolic risk factors such as triglycerides, HDL-cholesterol, blood pressure, fasting glucose and insulin, uric acid and C-reactive protein were measured. Receiver-operating characteristic (ROC) curves and logistic regression analyses were conducted.
Setting
Baltimore, Maryland.
Subjects
1,981 White and African-American US adults, aged 30-64 years.
Results
In predicting risk of MetS using obesity-independent National Cholesterol Education Program Adult Treatment Panel III criteria, % body fat mass (TtFM) assessed using DXA measuring overall adiposity had no added value over WC. This was true among both men (Areas under curve; AUC=0.680 vs. 0.733 for TtFM and WC, respectively, p<0.05) and women (AUC=0.581 vs. 0.686). Rib fat mass (RbFM) was superior to TtFM only in women for MetS (AUC=0.701 and 0.581 for RbFM and TtFM, respectively, p<0.05), particularly among African-American women. Elevated Leg fat mass (LgFM) was protective against MetS among African-American men. Among White men, BMI was inferior to WC in predicting MetS. Optimal WC cut points varied across ethnic-sex groups and differed from those recommended by the NIH/NAASO.
Conclusion
We provide evidence that WC is among the most powerful tools to predict MetS, and that optimal cut-points for various indices including WC may differ by sex and race.
doi:10.1017/S1368980010002648
PMCID: PMC3017668  PMID: 20854721
Metabolic syndrome; percent body fat mass; central obesity; body mass index
13.  Poverty, Race, and CKD in a Racially and Socioeconomically Diverse Urban Population 
Background
Low socioeconomic status (SES) and African American race are both independently associated with end-stage renal disease and progressive chronic kidney disease (CKD), however, despite their frequent co-occurrence, the effect of low SES independent of race has not been well-studied in CKD.
Study Design
Cross-sectional study.
Setting & Participants
2,375 community-dwelling adults age 30-64 years residing within 12 neighborhoods selected for both socioeconomic and racial diversity in Baltimore City, Maryland.
Predictors
Low SES [self-reported household income <125% of 2004 Department of Health and Human Services guideline], higher SES (≥125% of guideline); white and African American race.
Outcomes & Measurements
CKD defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Logistic regression used to calculate odds ratios (OR) for relationship between poverty and CKD, stratified by race.
Results
Of 2,375 participants; 955 were white (347 low SES and 608 higher SES); 1,420 were African American (713 low SES and 707 higher SES). A total of 146 (6.2%) participants had CKD. Overall, race was not associated with CKD [OR, 1.05; 95% confidence interval (CI), 0.57-1.96]; however, African Americans had a much greater odds of advanced CKD (eGFR <30 mL/min/1.73 m2). Low SES was independently associated with 59% greater odds of CKD after adjustment for demographics, insurance status and comorbid disease (OR, 1.59; 95% CI, 1.27-1.99). However, when stratified by race, low SES was associated with CKD in African Americans (OR, 1.91; 95% CI, 1.54-2.38), but not in whites (OR, 0.95; 95% CI, 0.58-1.55; P for interaction, 0.003).
Limitations
Cross-sectional design; findings may not be generalizable to non-urban populations.
Conclusions
Low SES has a profound relationship with CKD in African Americans but not in whites in an urban population of adults, and its role in the racial disparities seen in CKD is worthy of further investigation.
doi:10.1053/j.ajkd.2009.12.032
PMCID: PMC2876201  PMID: 20207457
Socioeconomic status; health disparities; epidemiology; renal disease
14.  Healthy food availability and the association with body mass index in Baltimore City, Maryland 
Public health nutrition  2011;14(6):1001-1007.
Objective
Previous literature has shown that the availability of healthy food in neighborhoods is associated with area characteristics and dietary quality. This study investigated the association between the availability of healthy foods and body mass index (BMI) among 2,616 participants living in Baltimore City.
Method
Trained staff collected demographic information, height, weight and 24-hr dietary recalls between 2004 and 2008. Healthy food availability was determined in 34 census tracts of varying racial and SES composition using the Nutrition Environment Measures Survey- Stores in 2007. Multilevel linear regression was used to estimate associations between healthy food availability and BMI.
Results
Among individuals living in predominately white neighborhoods, high availability of healthy foods was associated with significantly higher BMI compared to individuals living in low healthy food availability neighborhoods after adjustment for demographic variables (β=3.22, p=0.001). Associations were attenuated but remained significant after controlling for dietary intake (β=2.81, p=0.012).
Conclusion
Contrary to expectations, there was a positive association between the availability of healthy food and higher BMI among individuals living in predominately white neighborhoods. This result could be due to individuals in low healthy food availability areas traveling outside their neighborhood to obtain healthy food.
doi:10.1017/S1368980010003812
PMCID: PMC3089686  PMID: 21272422
Body mass index; Healthy Food Availability; Obesity; BMI; Neighborhood; Racial Composition; Socioeconomic Status
15.  Recruitment and Retention Strategies for Minority or Poor Clinical Research Participants: Lessons From the Healthy Aging in Neighborhoods of Diversity Across the Life Span Study 
The Gerontologist  2011;51(Suppl 1):S33-S45.
Purpose of the study: Investigating health disparities requires studies designed to recruit and retain racially and socioeconomically diverse cohorts. It is critical to address the barriers that disproportionately affect participation in clinical research by minorities and the socioeconomically disadvantaged. This study sought to identify and rectify these barriers to recruit and retain a biracial (African American and non-Hispanic White) and socioeconomically diverse cohort for a longitudinal study. Design and Method: The Healthy Aging in Neighborhoods of Diversity across the Life Span study is a 20-year longitudinal examination of how race and socioeconomic status influence the development of age-related health disparities. One goal was to create a multifactorial recruitment and retention strategy. The recruitment paradigm targeted known barriers and identified those unique to the study's urban environment. The retention paradigm mirrored the recruitment plan but was based on specifically developed approaches. Results: This cohort recruitment required attention to developing community partnerships, designing the research study to meet the study hypotheses and to provide benefit to participants, providing a safe community-based site for the research and creating didactics to develop staff cultural proficiency. These efforts facilitated study implementation and enhanced recruitment resulting in accrual of a biracial and socioeconomically diverse cohort of 3,722 participants. Implications: Recruiting and retaining minority or poor research participants is challenging but possible. The essential facets include clear communication of the research hypothesis, focus on providing a direct benefit for participants, and selection of a hypothesis that is directly relevant to the community studied
doi:10.1093/geront/gnr027
PMCID: PMC3092978  PMID: 21565817
Cultural proficiency; Health disparities; Community-based research platform
16.  A FLUORIMETRIC SEMI-MICROPLATE FORMAT ASSAY OF PROTEIN CARBONYLS IN BLOOD PLASMA 
Analytical biochemistry  2010;400(2):289-294.
Oxidative stress, originating from reactive oxygen species (ROS), has been implicated in aging and various human diseases. The ROS generated can oxidize proteins producing protein carbonyl derivatives. The level of protein carbonyls in blood plasma has been used as a measure of overall oxidative stress in the body. Classically, protein carbonyls have been quantitated spectrophotometrically by directly reacting them with 2,4, dinitrophenylhydrazine (DNPH). However, the applicability of this method to biological samples is limited by its low inherent sensitivity. This limitation has been overcome by the development of sensitive ELISA methods to measure protein carbonyls. As part of the Healthy Aging in Neighborhoods of Diversity across the Lifespan study, oxidative stress in humans were quantified by measuring blood plasma protein carbonyls using the two commercially available ELISA kits and the spectrophotometric DNPH assay. Surprisingly, two ELISA methods gave very different values for protein carbonyls that were both different from the spectrophotometric method. We have developed a fluorescent semi-microplate format assay of protein carbonyls involving direct reaction of protein carbonyls with fluorescein thiosemicarbazide that correlates (R=0.992) with the direct spectrophotometric method. It has a coefficient of variation of 4.99% and is at least 100 times more sensitive than the spectrophotometric method.
doi:10.1016/j.ab.2010.01.032
PMCID: PMC2843809  PMID: 20122892
Protein carbonyl; fluorescence; fluorimetric; assay; human plasma; fluorescein thiosemicarbazide; micro plate format
17.  Age, sex, and race influence single-strand break repair capacity in a human population 
Free radical biology & medicine  2008;45(12):1631-1641.
Recently, we developed an improved comet assay protocol for evaluating single-strand break repair capacity (SSB-RC) in unstimulated cryopreserved human peripheral blood mononuclear cells (PBMCs). This methodology facilitates control of interexperimental variability [A.R. Trzeciak, J. Barnes, M.K. Evans, A modified alkaline comet assay for measuring DNA repair capacity in human populations. Radiat. Res. 169 (2008) 110-121]. The fast component of SSB repair (F-SSB-RC) was assessed using a novel parameter, the initial rate of DNA repair, and the widely used half-time of DNA repair. The slow component of SSB repair (SSSB-RC) was estimated using the residual DNA damage after 60 min. We have examined repair of γ-radiation-induced DNA damage in PBMCs from four age-matched groups of male and female whites and African-Americans between ages 30 and 64. There is an increase in F-SSB-RC with age in white females (P<0.01) and nonsignificant decrease in F-SSB-RC in African-American females (P=0.061). F-SSB-RC is lower in white females than in white males (P<0.01). There is a decrease in F-SSB-RC with age in African-American females as compared to white females (P<0.002) and African-American males (nonsignificant, P=0.059). Age, sex, and race had a similar effect on intercellular variability of DNA damage in γ-irradiated and repairing PBMCs. Our findings suggest that age, sex, and race influence SSB-RC as measured by the alkaline comet assay. SSB-RC may be a useful clinical biomarker.
doi:10.1016/j.freeradbiomed.2008.08.031
PMCID: PMC3072751  PMID: 18845243
SSB repair capacity; SSB repair kinetics; DNA repair; Comet assay; γ-irradiation; Cryopreserved lymphocytes; Oxidative DNA damage; Reference standards; Biomonitoring study; Dispersion coefficient H; Coefficient of variation
18.  Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS): Overcoming barriers to implementing a longitudinal, epidemiologic, urban study of health, race, and socioeconomic status 
Ethnicity & disease  2010;20(3):267-275.
Objective
Examine the influences of race, socioeconomic status, sex, and age on barriers to participation in a study of cross-sectional differences and longitudinal changes in health-related outcomes.
Methods
We designed a multidisciplinary, community-based, prospective longitudinal epidemiologic study among socioeconomically diverse African Americans and whites. The study protocol facilitated our ability to recruit 3722 participants from Baltimore, MD with mean age 47.7 (range 30–64) years, % males/female, 2200 African Americans (59%) and 1522 whites (41%); 41% reported household incomes below the 125% poverty delimiter.
Results
There were no significant age differences associated with sex or race. Participants below the 125% poverty delimiter were slightly younger than those above the delimiter. Age, race, and sex, but not poverty status, were associated with the likelihood of an examination. Older participants, women, and whites were more likely to complete their examinations. Among those who completed their examinations, there were no age differences associated with sex and poverty status, but African Americans were negligibly younger than whites.
Conclusions
Although some literature suggests that minorities and low-income people are less willing to participate in clinical research, these baseline data suggest that African Americans individuals and individuals from households with incomes below 125% of the poverty level are at least as willing to participate in observational clinical studies as whites and higher income individuals of similar age and sex.
PMCID: PMC3040595  PMID: 20828101
Healthcare disparities; socioeconomic status; Population groups; Epidemiologic research design; Health surveys; Longitudinal studies
19.  The effect of race and predictors of socioeconomic status on diet quality in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study sample 
Purpose
To examine effects of race and predictors of socioeconomic status (SES) on nutrient-based diet quality and their contribution to health disparities in an urban population of low SES.
Design
Data were analyzed from a sample of the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) Study participants examining effects of age, sex, race, income, poverty income ratio (PIR), education, employment, and smoking status on nutrient-based diet quality as measured by a micronutrient composite index of nutrient adequacy ratios (NAR) and a mean adequacy ratio (MAR). Regression models were used to examine associations and t-tests were used to look at racial differences.
Subjects
African American and white adults ages 30-64 residing in 12 predefined census tracts in Baltimore City, Maryland.
Results
Sex, age, education, PIR, and income were statistically significant predictors of diet quality for African Americans, while sex, education, and smoking status were statistically significant for whites. African Americans had lower MAR scores than whites (76.4 vs. 79.1). Whites had significantly higher NAR scores for thiamin, riboflavin, folate, B12, vitamins A and E, magnesium, copper, zinc, and calcium, while African Americans had higher vitamin C scores.
Conclusion
Education significantly impacted diet quality in the HANDLS sample, but race cannot be discounted. Whether the racial differences in diet quality are indicative of cultural differences in food preferences, selection, preparation, and availability or disparities in socioeconomic status remains unclear.
PMCID: PMC2987681  PMID: 21053707
Race; Socioeconomic Status; Education; Diet Quality
20.  Beverage Consumption Patterns of a Low-Income Population 
Topics in clinical nutrition  2010;25(3):191-201.
High-energy-dense foods provide an inexpensive source of calories. Healthy Aging in Neighborhoods of Diversity across the Life Span study participants (n = 1987), low- to low-middle-income, urban African American and white adults, consumed between 17% and 20% of their daily energy intake from beverages. Of all beverages consumed, calorically sweetened beverages ranked second among African Americans and third among whites. Calorically-sweetened beverage consumption was not influenced by weight status. Increasing awareness of risks for adverse health outcomes associated with selected beverages may improve dietary choices.
PMCID: PMC2957908  PMID: 20976036
energy intake; obesity
21.  Effects of Race and Socioeconomic Status on the Relative Influence of Education and Literacy on Cognitive Functioning 
Previous research has shown that reading ability is a stronger predictor of cognitive functioning than years of education, particularly for African Americans. The current study was designed to determine whether the relative influence of literacy and education on cognitive abilities varies as a function of race or socioeconomic status (SES). We examined the unique influence of education and reading scores on a range of cognitive tests in low and high SES African Americans and Whites. Literacy significantly predicted scores on all but one cognitive measure in both African American groups and in low SES Whites, while education was not significantly associated with any cognitive measure. In contrast, both education and reading scores predicted performance on many cognitive measures in high SES Whites. These findings provide further evidence that reading ability better predicts cognitive functioning than years of education and suggest that disadvantages associated with racial minority status and low SES affect the relative influence of literacy and years of education on cognition.
doi:10.1017/S1355617709090821
PMCID: PMC2722437  PMID: 19573276
reading; income; demographics; ethnicity; neuropsychological testing; cognition
22.  microRNA Expression Patterns Reveal Differential Expression of Target Genes with Age 
PLoS ONE  2010;5(5):e10724.
Recent evidence supports a role for microRNAs (miRNAs) in regulating the life span of model organisms. However, little is known about how these small RNAs contribute to human aging. Here, we profiled the expression of over 800 miRNAs in peripheral blood mononuclear cells from young and old individuals by real-time RT-PCR analysis. This genome-wide assessment of miRNA expression revealed that the majority of miRNAs studied decreased in abundance with age. We identified nine miRNAs (miR-103, miR-107, miR-128, miR-130a, miR-155, miR-24, miR-221, miR-496, miR-1538) that were significantly lower in older individuals. Among them, five have been implicated in cancer pathogenesis. Predicted targets of several of these miRNAs, including PI3 kinase (PI3K), c-Kit and H2AX, were found to be elevated with advancing age, supporting a possible role for them in the aging process. Furthermore, we found that decreasing the levels of miR-221 was sufficient to cause a corresponding increase in the expression of the predicted target, PI3K. Taken together, these findings demonstrate that changes in miRNA expression occur with human aging and suggest that miRNAs and their predicted targets have the potential to be diagnostic indicators of age or age-related diseases.
doi:10.1371/journal.pone.0010724
PMCID: PMC2873959  PMID: 20505758
23.  Deficient repair of 8-hydroxyguanine in the BxPC-3 pancreatic cancer cell line 
Elevated levels of oxidatively induced DNA lesions have been reported in malignant pancreatic tissues relative to normal pancreatic tissues. However, the ability of the pancreatic cancer cells to remove these lesions has not previously been addressed. This study analyzed the effectiveness of the pancreatic cancer cell line, BxPC-3 to repair 8-hydroxyguanine (8-OH-Gua) relative to a nonmalignant cell line. We show that BxPC-3 cells repair 8-OH-Gua less effectively than the nonmalignant cells. This repair deficiency correlated with significant downregulation of the hOGG1 protein and the corresponding mRNA (30-fold lower than GAPDH) in BxPC-3 cell line. The repair defect was complemented in vivo by transient transfection of the hOGG1 gene and in vivo by recombinant hOGG1. These results are the first to show a deficiency of 8-OH-Gua repair in BxPC-3 cells, implicating this defect in the risk factor of pancreatic cancer.
doi:10.1016/j.bbrc.2008.08.134
PMCID: PMC2699024  PMID: 18774780
Pancreatic cancer; Oxidative stress; Oxidative DNA damage; DNA repair; Base excision repair; Reactive oxygen species; 8-Hydroxyguanine; hOGG1; Pancreatic cancer risk and antioxidant; enzymes
24.  Personality Traits and Sex Differences in Emotions Recognition Among African Americans and Caucasians 
PMCID: PMC2580736  PMID: 14766644
emotion recognition; personality traits; openness; sex differences; cross; cultural
25.  Reduced repair of 8-hydroxyguanine in the human breast cancer cell line, HCC1937 
BMC Cancer  2006;6:297.
Background
Breast cancer is the second leading cause of cancer deaths in women in the United States. Although the causes of this disease are incompletely understood, oxidative DNA damage is presumed to play a critical role in breast carcinogenesis. A common oxidatively induced DNA lesion is 8-hydroxyguanine (8-OH-Gua), which has been implicated in carcinogenesis. The aim of this study was to investigate the ability of HCC1937 and MCF-7 breast cancer cell lines to repair 8-OH-Gua relative to a nonmalignant human mammary epithelial cell line, AG11134.
Methods
We used oligonucleotide incision assay to analyze the ability of the two breast cancer cell lines to incise 8-OH-Gua relative to the control cell line. Liquid chromatography/mass spectrometry (LC/MS) was used to measure the levels of 8-OH-Gua as its nucleoside, 8-OH-dG in the cell lines after exposure to H2O2 followed by 30 min repair period. Protein expression levels were determined by Western blot analysis, while the hOGG1 mRNA levels were analyzed by RT-PCR. Complementation of hOGG1 activity in HCC1937 cells was assessed by addition of the purified protein in the incision assay, and in vivo by transfection of pFlagCMV-4-hOGG1. Clonogenic survival assay was used to determine sensitivity after H2O2-mediated oxidative stress.
Results
We show that the HCC1937 breast cancer cells have diminished ability to incise 8-OH-Gua and they accumulate higher levels of 8-OH-dG in the nuclear genome after H2O2 treatment despite a 30 min repair period when compared to the nonmalignant mammary cells. The defective incision of 8-OH-Gua was consistent with expression of undetectable amounts of hOGG1 in HCC1937 cells. The reduced incision activity was significantly stimulated by addition of purified hOGG1. Furthermore, transfection of pFlagCMV-4-hOGG1 in HCC1937 cells resulted in enhanced incision of 8-OH-Gua. HCC1937 cells are more sensitive to high levels of H2O2 and have up-regulated SOD1 and SOD2.
Conclusion
This study provides evidence for inefficient repair of 8-OH-Gua in HCC1937 breast cancer cell line and directly implicates hOGG1 in this defect.
doi:10.1186/1471-2407-6-297
PMCID: PMC1770930  PMID: 17192190

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